This research is directed at continuing our studies aimed at generating cytotoxic lymphocytes in vitro capable of lysing autologous human leukemia cells by culturing remission lymphocytes with (a) X-irradiated autologous leukemia cells and X-irradiated allogeneic normal cells or with (b) X-irradiated lymphocytes pooled from 20 unrelated normal individuals. Highly purified interferon (IF) and nontoxic polyribonucleotide inducers of IF also will be tested for their ability to activate patients' remission lymphocytes to lyse autologous malignant cells. Effector cells will be characterized with regard to expression of cell surface antigens by monoclonal antibodies, which we have found distinguish cytotoxic T lymphocytes (CTLs) from natural killer (NK) and NK-like cells. We propose to generate large numbers of antileukemia effector cells by growing sensitized cells in T-cell growth factor (TCGF) and to clone these cells to test their specificity. In addition, we propose to continue our studies of human NK and CTL-mediated lysis of autologous cells infected with herpes simplex virus that can produce severe infections in leukemia and lymphoma patients. We have found that conventional NK cells lyse autologous HSV-infected cells and that NK (HSV) activity is depressed in patients who continuously shed virus. We have begun cloning CTL against HSV-infected cells and are studying the nature of the HLA restriction and the virus type specificity of the clones.